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Effects on fertility

Description of key information

A study performed in 2009 by the U.S. Army Center for Health Promotion and Preventive Medicine following the guidance USEPA OPPTS 870.3550 Reproduction/Developmental Toxicity Screening Test demostrated that rats (10 male and 10 female) orally dosed 100, 500 and 1000 mg/kg for 56 days did not show any effects on their reproductive performance. Due to explosive properties of the substance, no further testing could be conducted.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
other: USEPA OPPTS 870.3550 Reproduction/Developmental Toxicity Screening Test
GLP compliance:
yes
Remarks:
This study was conducted consistent with the standards found in Title 40 US Code of Federal Regulations (CFR), Part 792, Good Laboratory Practices.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
56 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:0 mg PETN/kgBasis:nominal in diet
Remarks:
Doses / Concentrations:100 mg PETN/kgBasis:nominal in diet
Remarks:
Doses / Concentrations:500 mg PETN/kgBasis:nominal in diet
Remarks:
Doses / Concentrations:1000 mg PETN/kgBasis:nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes
Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: at least once a day, and more frequently when signs of toxicity are observed. The duration of gestation was recorded and calculated from day 0 of pregnancyBODY WEIGHT: Yes - Time schedule for examinations: Males and females were individually weighed the day before and on the first day of dosing, weekly thereafter, and at termination of the study.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
Sperm parameters (parental animals):
PARAMETERS EXAMINED IN [MALE PARENTAL GENERATIONS [testis weight, epididymis weight, daily sperm production, sperm count in testes, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology, other:]
Litter observations:
Each litter was examined as soon as possible after delivery to establish the number and sex of pups,still births, live births, and runts (pups that are significantly smaller than corresponding control pups), and the presence of gross abnormalities. Live pups were counted and sexed, and litters weighed within 24 hr of parturition (day 1) and on day 4 post-partum.
Postmortem examinations (parental animals):
SACRIFICE: No rats died due to PETN toxicityGROSS NECROPSY: animals were examined for any abnormalities or pathological changes, with special attention being paid to the reproductive organs.HISTOPATHOLOGY / ORGAN WEIGHTS: Testes, epididymides, and ovaries were fixed in Bouin�s fixative, embedded in paraffin, cut into transverse sections of 4�5 mm thickness, and stained with PAS and hematoxylin.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Dose descriptor:
NOAEC
Effect level:
>= 1 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Clinical signs:
effects observed, non-treatment-related
Dermal irritation (if dermal study):
not examined
Mortality / viability:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
dose level: Pups received PETN only through lactation.
Generation:
F1
Effect level:
> 100 - < 500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
Reproductive effects observed:
not specified
Conclusions:
No adverse effects on development or reproduction from PETN exposure were observed.
Executive summary:

Sprague-Dawley rats were exposed to oral daily adjusted volumetric doses of 0, 100, 500, or 1,000mg PETN/kg body mass in a corn oil vehicle for up to 56 days. Mating, duration of gestation, body weight, feed consumption, overall condition of adults, and the number, sex, and condition of pups were recorded. Histological examinations were also performed on the ovaries, testes, and epididymides of animals from the control and the highest dose groups. Only body weights

and feed consumption were affected by treatment; however, these differences may be attributed more to volumetric adjustments of vehicle in the control and high-dose groups than to PETN toxicity. No adverse effects on development or reproduction from PETN exposure were observed.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Due to explosive properties of the substance, the performance of this test is highly advised against.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

PETN is a sensitive compound and is easily detonated by an appropriate mechanical shock or when it is exposed to heat. Submitting the substance to testing would pose an extreme risk to the laboratory personnel and facilities due to explosive nature of the substance.

Justification for classification or non-classification

Reliable information on toxicity for reproduction shows a NOAEL of > 1000 mg/kg bw/day. No classification is proposed based on the results obtained from studies performed.

Additional information

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